Thin-Layer Chromatography on Reversed Phase in the Characterization of Retention Behaviour, Lipophilicity, and Pharmacokinetics of Cyanoacetamide Derivatives

Abstract

Biological activity of a molecule is closely related to its lipophilicity. This significant parameter was determined for a group of potentially bioactive N-(4-phenylmonosubstituted)-2-cyanoacetamides applying thin-layer chromatography on reversed phase (RP-TLC) in mixtures of water and two organic modifiers separately, i-propanol and dioxane. The effect of the chemical structure of derivatives and the influence of the applied organic modifier on their retention were studied. The determined chromatographic retention constants, RM 0 , and the chromatographic parameter, m, of compounds were correlated with software calculated partition coefficients, log P as the standard measure of lipophilicity and with different pharmacokinetic predictors applying classical linear and multiple regression analysis. By classical linear regression analysis in both water-modifier systems only RM 0-log P and m-log P correlations were established (average r, 0.909 and 0.826). All studied relationships were enhanced by molecular descriptors that fulfilled the modified Lipinski's rule of five. Thereby, the performed multiple regression analysis gave better correlations (for RM 0-log P and m-log P average r 2 , 0.994 and 0.993; for RM 0-pharmacokinetic parameters and m-pharmacokinetic parameters average r 2 0.978 and 0.980). The obtained results indicate that the chromatographic parameters, RM 0 and m determined by RP-TLC at given conditions could be used successfully for the description of lipophilicity and the evaluation of pharmacokinetic properties of N-(4-phenylmonosubstituted)-2-cyanoacetamides as potential bioactive molecules.

Evaluation of the Usefulness of Topological Indices for Predicting Selected Physicochemical Properties of Bioactive Substances with Anti-Androgenic and Hypouricemic Activity

“…Many research studies have been conducted in this area in recent years [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. Numerous published QSAR and QSPR models include lipophilicity parameters obtained by thin-layer chromatography and highperformance liquid chromatography in a reversed phase system, i.e., RP-TLC or RP-HPLC as R MW and logk w values, respectively or using computational approaches in the form of logP [27][28][29][30][31][32][33]. The chromatographic analysis is rapid and repeatable and until today has been suitable for the study of lipophilicity of different classes of bioorganic compounds [27][28][29][30][31][32][33].…”

A Comparative Study of the Lipophilicity of Metformin and Phenformin

“…Chromatographically determined parameters R MW and logk w are powerful lipophilicity descriptors [1]. Numerous studies have been performed in order to determine the lipophilic properties of different bioactive compounds as drugs or new drug candidates, including the new purine-2,6-dione derivatives, newly synthesized celecoxib analogues, thiosemicarbazides, quinolone sulfonamides, benzenesulfonohydrazides, 1,2,3-triazoledipyridothiazine hybrids, betulin derivatives, selected steroid derivatives, chalcones, and flavonoids, by using liquid chromatographic techniques, including RP-TLC [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Among various chromatographic separation methods, RP-TLC is an easy-to-use and low-cost chromatographic technique.…”